Global prevalence of cervical human papillomavirus in women aged 50 years and older with normal cytology: a systematic review and meta-analysis.

Background: Given the paucity of up-to-date empirical data on human papillomavirus (HPV) among older women, we aimed to estimate the global HPV prevalence in women aged 50 years and older with normal cytology.

Methods: In this systematic review and meta-analysis, we searched for quantitative studies (cross-sectional, longitudinal, case-control, randomised control trials) reporting HPV prevalence among women aged 50 years and older with normal cytology published until May 31, 2022, in PubMed, Scopus, and Web of Science. The risk of bias was assessed using a modified Newcastle-Ottawa scale. The pooled prevalence and 95% CIs of any-HPV and high-risk (HR)-HPV were estimated using random-effects models. Geographical differences were assessed in stratified meta-analyses and multiple meta-regression models. The prevalence by 5-year age groups and genotypes was estimated when reported using mixed-effects models. The study protocol was registered with PROSPERO (CRD42021241365).

Findings: From 9099 identified articles, 132 were included in the qualitative synthesis. 91 (68·9%) studies were deemed to have a low risk of bias and 41 (31·1%) a high risk of bias. We estimated a worldwide pooled any-HPV prevalence of 11·70% (95% CI 9·68-13·87) from 73 studies including 41 745 women and an HR-HPV prevalence of 6·45% (5·45-7·53) from 102 studies including 437 228 women. The pooled prevalence varied geographically, with the highest estimates in western Africa (any-HPV: 32·26% [4·53-70·22]; HR-HPV: 16·20% [0·70-45·95]) and central America (any-HPV: 24·50% [9·97-42·93]; HR-HPV: 13·52% [9·48-18·14]), and the lowest in western Europe (any-HPV: 5·98% [3·08-9·77]; HR-HPV: 4·09% [2·37-6·25]) and western Asia (for HR-HPV only: 3·27% [0·00-20·91]). Worldwide, any-HPV prevalence generally decreased with age, from 10·74% (5·84-18·95) at 50-54 years to 3·56% (2·33-5·40) after age 75 years. HR-HPV prevalence decreased from 6·04% (4·33-8·38) at age 50-54 years to 4·61% (3·25-6·51) at 60-64 years, increased again to 6·33% (4·03-9·79) at 65-69 years, and then decreased to 5·28% (2·83-9·63) after age 75 years. HPV types 16 (1·17% [0·67-2·03]) and 53 (0·90% [0·43-1·90]) were the most prevalent globally.

Interpretation: HPV prevalence in women aged 50 years and older with normal cytology varies globally and mostly correlates with the cervical cancer burden. Research on HPV persistence, progression, and cost-effectiveness of HPV testing among older women should be conducted to fully inform future cervical cancer screening policies.

Funding: None.